Date Published: December 10, 2019
Publisher: Springer International Publishing
Author(s): Brian Booth, Faye Vazvaei, Eric Fluhler, Heather Myler, Eric Woolf.
Over the last decade, several regulatory guidelines on bioanalytical method validation (BMV) have been issued by regulatory agencies around the world. This has left the bioanalytical community struggling with regional differences in regulatory expectations when preparing for global pharmaceutical submissions. The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) has the mission to achieve greater harmonization worldwide to ensure that safe, effective, and high-quality medicines are developed and registered in the most resource-efficient manner. Following calls for harmonization, ICH-selected bioanalytical method validation and sample analysis among its topics for guidance development and earlier this year released a draft guideline (M10) on BMV for public consultation. In response, the American Association of Pharmaceutical Scientists (AAPS) held a 3-day workshop to provide a forum for regulatory, industry, and academic scientists to discuss the guideline and hear various points of view on key aspects. While there was agreement that the draft guideline is generally well written and comprehensive, specific topics generated considerable discussion and, in some cases, revision recommendations for consideration by the expert working group (EWG) responsible for the guideline content. This report provides a summary of the workshop proceedings.
In February 2019, the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) released a draft harmonized guideline (M10) on bioanalytical method validation (BMV) for public consultation. In its continuing efforts to support excellence in the pharmaceutical sciences, the American Association of Pharmaceutical Scientists (AAPS), in collaboration with the European Bioanalysis Forum (EBF), Japan Bioanalysis Forum (JBF), and China Bioanalysis Forum (CBF), organized a workshop for stakeholders from industry, academia, and health authorities to discuss and provide collective feedback on the draft guideline. This was the second in a series of sister workshops organized by the previously mentioned regional bioanalytical groups. The first forum in this series, organized by EBF, was held in May 2019 in Barcelona, Spain.
It has long been recognized that bioanalysis plays an important, even critical, role in drug development and the regulatory approval process. Aiming to ensure that the best scientific practices are embraced, the bioanalytical community (industry, academic, and health authority scientists) has been actively engaged in discussions of best practices over the years. In the USA, this dialogue has, to a large extent, taken the form of multiday workshops. AAPS and the FDA have co-sponsored several of these workshops (commonly referred to as the Crystal City Meetings), the outputs of which were published (1–5) and served as substrate for consideration in development and revision of FDA regulatory guidance. (6,7) While the 2001 FDA guidance on BMV served as an industry benchmark for chromatographic assays for several years, numerous health authorities have since published their own guidelines (e.g., ANVISA 2003/2012, EMA in 2011, MHLW in 2013/2014, and the China Pharmacopeia in 2015) (8–13), in some cases including expectations for both chromatographic and ligand-binding assays. Although these guidance/guidelines share many of the same basic principles and requirements, important differences do exist. As a result, sponsors must consider the implications of these differences on global submissions, often resulting in additional work. This has led to a general call for harmonization of the various BMV guidance/guidelines (14), and in 2016, ICH announced it had endorsed “BMV and sample analysis” as a topic for development of a new guideline (M10). Following endorsement, an expert working group (EWG) with representatives from ICH member health authorities and industry organizations (e.g., PhRMA, EFPIA) was assembled and tasked with authoring the draft ICH M10 BMV guideline. The draft guideline was posted for public consultation in February 2019. In keeping with its tradition of supporting the bioanalytical community, AAPS organized a workshop, held in June 2019, to discuss the guideline, allow participants to hear both industry and health authority perspectives, and ultimately, provide collective feedback to the EWG. The meeting also offered the opportunity for participants to hear a summary of a similar “sister” meeting held by the EBF and comments provided by CBF and JBF leadership/representatives. The following sections summarize the deliberations which took place during each day of the workshop, with emphasis on topics that generated the most discussion.
This session included an introduction to the workshop and the historical landscape leading up to the M10 draft. The session also dealt with the objective, background, and scope of the guideline and the section on method development.
Day two of the workshop was kicked off with a summary of the consensus from day one. Immediately after, the discussions started, beginning with the topic of stability, followed by sample analysis and analytical run.
This session dealt with the topics of reanalysis (including ISR), analytes that are also endogenous, diagnostic kits, method validation to support new modalities, and documentation.
In the concluding session of the workshop, representatives from “sister” bioanalytical organizations (EBF, CBF, and JBF) presented the outcomes of the discussions of their respective organizations on the M10 draft. Recommendations of these organizations generally mirrored those reached by workshop participants. None of the proposals of these organizations were in direct conflict with those of this workshop. In addition, several points that were only briefly touched upon during the workshop were explicitly mentioned by these groups.
The 2.5-day workshop permitted robust discussion on the majority of the concerns of industry on the M10 draft. As a result of the workshop, AAPS has submitted the proposals upon which consensus was reached to the FDA through the website that they have established to receive comments on M10. It is hoped that these will be reviewed by members of the M10 EWG and that the final version of M10 will take these into account.